Alimu Ayiguli, Abudureman Haiqiemuhan, Wang Yong-Zhi, Li Mei-Yan, Wang Jia-Sui, Liu Zao-Ling
Department of Epidemiology and Health Statistics, School of Public Health, Xinjiang Medical University, Urumqi 0991, Xinjiang Uygur Autonomous Region, China.
Department of Public Health, Xinjiang Second Medical College, Cremayi 834000, Xinjiang Uygur Autonomous Region, China.
World J Diabetes. 2021 Aug 15;12(8):1267-1281. doi: 10.4239/wjd.v12.i8.1267.
Decabromodiphenyl ether (BDE-209) is the most commonly used brominated flame retardant. Recently, BDE-209 has been suspected of being an environmental risk factor for metabolic diseases such as obesity, insulin resistance (IR), type 2 diabetes mellitus, and hypertension.
To investigate the effects of BDE-209 on IR and glucose and lipid metabolism in C57BL/6 mice.
Adult male C57BL/6 mice were randomly divided into high, medium-high, medium, medium-low, and low dose BDE-209 groups, and a control group ( = 6 per group), which received 1000, 800, 600, 450, 300, and 0 mg/kg BDE-209, respectively. After BDE-209 exposure for 60 d, the mice were fasted overnight, and then sacrificed to obtain tissues. An automatic biochemical analyzer was used to detect serum triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high density lipoprotein cholesterol (HDL-C); enzyme-linked immunosorbent assay kits were used to detect fasting serum insulin (FINS), leptin (LEP), and adiponectin (Adp) levels; a blood glucose meter was used to detect fasting blood glucose (FBG). Morphological changes of the liver were observed by hematoxylin and eosin staining. Real-time quantitative polymerase chain reaction and Western blot were used to determine the messenger ribonucleic acid (mRNA) and protein levels, respectively, of LEP, Adp, and peroxisome proliferators activated receptor-γ (PPARγ) in mouse liver and adipose tissues.
There was a statistically significant difference in the weight of mice in each group after 45 and 60 d of exposure ( < 0.05). After 60 d of exposure, the weight of liver and adipose tissues in the exposure groups were greater than that of the control group ( < 0.05). The liver tissue structure was disordered and the liver tissues were accompanied by local inflammatory cell infiltration in the high, medium-high, and medium dose BDE-209 groups. The levels of FINS, insulin sensitivity index, Adp, and HDL-C were decreased in the BDE-209 group compared with the control group, as were the mRNA and protein levels of Adp in liver and adipose tissues ( < 0.05). Serum level of FBG and LEP were higher in the BDE-209 group than in controls. TC, TG, and LDL-C levels as well as the mRNA and protein expression of LEP and PPARγ in liver and adipose tissues were higher than those in the control group ( < 0.05). Homeostatic assessment model of IR was higher in the medium and medium-low dose BDE-209 groups ( < 0.05).
BDE-209 increases the body weight, fat and liver tissue weight, TC, TG, and LDL-C, reduces HDL-C, and causes IR in mice, which may be related to activating the PPARγ receptor.
十溴二苯醚(BDE - 209)是最常用的溴化阻燃剂。最近,BDE - 209被怀疑是肥胖、胰岛素抵抗(IR)、2型糖尿病和高血压等代谢性疾病的环境风险因素。
研究BDE - 209对C57BL/6小鼠胰岛素抵抗及糖脂代谢的影响。
将成年雄性C57BL/6小鼠随机分为高、中高、中、中低、低剂量BDE - 209组和对照组(每组n = 6),分别给予1000、800、600、450、300和0 mg/kg的BDE - 209。BDE - 209暴露60 d后,小鼠禁食过夜,然后处死获取组织。用自动生化分析仪检测血清甘油三酯(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL - C)和高密度脂蛋白胆固醇(HDL - C);用酶联免疫吸附测定试剂盒检测空腹血清胰岛素(FINS)、瘦素(LEP)和脂联素(Adp)水平;用血糖仪检测空腹血糖(FBG)。通过苏木精-伊红染色观察肝脏的形态学变化。采用实时定量聚合酶链反应和蛋白质免疫印迹法分别测定小鼠肝脏和脂肪组织中LEP、Adp和过氧化物酶体增殖物激活受体γ(PPARγ)的信使核糖核酸(mRNA)和蛋白质水平。
暴露45 d和60 d后,各组小鼠体重差异有统计学意义(P < 0.05)。暴露60 d后,暴露组肝脏和脂肪组织重量均大于对照组(P < 0.05)。高、中高和中剂量BDE - 209组肝组织结构紊乱,伴有局部炎症细胞浸润。与对照组相比,BDE - 209组FINS、胰岛素敏感指数、Adp和HDL - C水平降低,肝脏和脂肪组织中Adp的mRNA和蛋白质水平也降低(P < 0.05)。BDE - 209组血清FBG和LEP水平高于对照组。TC、TG和LDL - C水平以及肝脏和脂肪组织中LEP和PPARγ的mRNA和蛋白质表达均高于对照组(P < 0.05)。中、中低剂量BDE - 209组的IR稳态评估模型较高(P < 0.05)。
BDE - 209可增加小鼠体重、脂肪和肝脏组织重量,升高TC、TG和LDL - C,降低HDL - C,并导致小鼠胰岛素抵抗,这可能与激活PPARγ受体有关。